Rheumatology Advance Access published online on May 15, 2007
Rheumatology, doi:10.1093/rheumatology/kem096
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Caspase 7 influences susceptibility to rheumatoid arthritis
Servicio de Inmunología. Hospital Universitario Virgen del Rocío, Sevilla, 1Instituto de Parasitología y Biomedicina ‘López Neyra’, Granada, 2Servicio de Reumatología, Hospital Universitario Virgen del Rocío, Sevilla, 3Servicio de Reumatología, Hospital Xeral-Calde, Lugo and 4Servicio de Reumatología, Hospital Virgen de las Nieves, Granada
Correspondence to:
M. F. González-Escribano, Servicio de Inmunología, H. U. Virgen del Rocío, Avda Manuel Siurot s/n, 41013 Sevilla, Spain. E-mail: mariaf.gonzalez.sspa{at}juntadeandalucia.es
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Abstract |
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Objective. The aim of this study was to investigate the possible role of the caspase 7 (CASP7 ) in susceptibility to rheumatoid arthritis (RA).
Methods. Genotyping of three single nucleotide polymorphisms (SNPs) of the CASP7 gene: rs11593766 (G/ T), rs2227310 (C/G) and rs2227309 (G/A) was performed in a total of 906 RA patients and 528 matched healthy controls using TaqMan assays. All the subjects were of Spanish Caucasian origin. A relative quantification of mRNA encoding the non-functional variant of procaspase 7 (isoform ß) vs functional isoforms was performed in total RNA from 32 healthy individuals using real-time PCR.
Results. Only the rs2227309 SNP was found to be associated with susceptibility to RA. Frequency of the G allele was significantly higher among RA patients [overall frequency of the G allele 74.0% in cases vs 68.4% in controls, P = 0.001, Odds ratio (OR) = 1.32, 95% Confidence intervals (95% CI) 1.11–1.56] and a higher frequency of GG homozygous individuals was found in the RA patient group (overall frequency of GG genotype 56.0% in cases and 46.4% in controls, P = 0.0005, OR = 1.47, 95%CI 1.18–1.83). A statistically significant deviation was observed to compare the relative expression of the procaspase 7 isoform ß in samples from individuals stratified according their rs2227309 genotypes (AA + AG: 1.36 ± 0.55, n = 19, vs GG: 2.35 ± 0.74, n = 13; P = 0.0002).
Conclusion. Our results support involvement of the CASP7 gene in the susceptibility to RA. The higher production of the no functional variant of CASP7 by individuals with a particular genotype could be the basis of this association.
KEY WORDS: Caspase 7, Rheumatoid arthritis, Polymorphism, Gene expression
*These authors share senior authorship in this study.
Submitted 18 December 2006;
revised version accepted 21 March 2007.
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